Resiquimod

• CAT Number: I001738
• CAS Number: 144875-48-9
• Molecular Formula: C17H22N4O2
• Molecular Weight: 314.4
• Purity: ≥95%
• Synonyms: 1-[4-amino-2-(ethoxymethyl)imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol
• Target: TLR
• Solubility: DMSO: ≥ 40 mg/mL
• Storage: Store at -20°C
• InChI: InChI=1S/C17H22N4O2/c1-4-23-9-13-20-14-15(21(13)10-17(2,3)22)11-7-5-6-8-12(11)19-16(14)18/h5-8,22H,4,9-10H2,1-3H3,(H2,18,19)
• InChIKey: BXNMTOQRYBFHNZ-UHFFFAOYSA-N
• SMILES: CCOCC1=NC2=C(N1CC(C)(C)O)C3=CC=CC=C3N=C2N

Resiquimod(CAT: I001738) is a small molecule agonist of Toll-like receptor 7 (TLR7) and TLR8, which are proteins involved in the innate immune response. It is a synthetic derivative of the natural product imiquimod and is used as a topical medication for the treatment of various skin conditions, including actinic keratosis, superficial basal cell carcinoma, and genital warts caused by human papillomavirus (HPV). Resiquimod works by activating the immune system to produce cytokines and chemokines, which in turn stimulate immune cells to attack the abnormal cells causing the skin condition. It has also been studied as a potential adjuvant therapy for cancer immunotherapy, as it can stimulate the immune system to recognize and attack cancer cells.

Overview of Clinical Research

Resiquimod is a Toll-like receptor 7/8 agonist, which is in the phase II study in Malignant melanoma.

Reference

1. Expert Opin Investig Drugs. 2013 Jan;22(1):149-59. doi: 10.1517/13543784.2013.749236. Epub 2012 Dec 4.

Resiquimod, a topical drug for viral skin lesions and skin cancer.

Meyer T(1), Surber C, French LE, Stockfleth E.
Author information:
(1)University of Hamburg, Institute of Medical Microbiology, Virology and Hygiene, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
INTRODUCTION: Resiquimod is an immune response modifier which stimulates cells through a toll-like receptors (TLR) 7 and 8 dependent pathway resulting in activation of immune responses that are effective against viral and tumor lesions.
AREAS COVERED: Studies on genital herpes, hepatitis C and actinic keratosis (AK) as well as papers of molecular activities of resiquimod were identified by a PubMed search. Although effective against genital HSV-2 in animal models, development of topical resiquimod for the treatment of recurrent genital herpes in humans was stopped due to inconsistent results in clinical trials. Reduction of HCV viral load was achieved by oral application but was associated with unacceptable side effects. Topical treatment of AK was well tolerated and effective with clearance rates higher compared to imiquimod. The molecular mode of action underlying the clinical efficacy primarily depends on cytokine induction in TLR7/8 expressing dendritic cells in the skin. EXPERT OPINION: Topical resiquimod was shown to be a safe and effective treatment option for AK and appears to have potential as a treatment modality for patients with extended skin areas affected with AK (field cancerization). Resiquimod may also have potential for the therapy or prevention of epithelial viral infections.

2. Expert Rev Vaccines. 2007 Oct;6(5):835-47.

Resiquimod and other immune response modifiers as vaccine adjuvants.

Tomai MA(1), Miller RL, Lipson KE, Kieper WC, Zarraga IE, Vasilakos JP.
Author information:
(1)3M Drug Delivery Systems, 3M Center, 275-3E-10 St Paul, MN 55144, USA.
Synthetic immune response modifiers, such as resiquimod, are Toll-like receptor 7 and 8 agonists that act as vaccine adjuvants, enhancing antigen-specific antibody production and skewing immunity towards a Th1 response. These compounds stimulate dendritic cells to secrete cytokines, upregulate costimulatory molecule expression and enhance antigen presentation to T cells. The compounds have demonstrated vaccine adjuvant properties in a number of animal models. The adjuvant effects can be enhanced by measures that allow the drug to stay localized with the vaccine without quickly entering the systemic circulation. Clinical studies demonstrate that topical application of resiquimod and analogs is safe and effective at activating the local immune response. For injection, resiquimod or a similar compound may need to be formulated to allow for local immune activation without induction of systemic cytokines.

3. Antiviral Res. 2004 Nov;64(2):79-83.

Resiquimod: a new immune response modifier with potential as a vaccine adjuvant for Th1 immune responses.

Wu JJ(1), Huang DB, Tyring SK.
Author information:
(1)Department of Dermatology, University of California, Irvine, Irvine, CA, USA.
Genital herpes is one of the most common sexually transmitted diseases worldwide. Currently, there are three FDA-approved nucleoside analogs and other therapies such as foscarnet and cidofovir used to treat genital herpes. Resiquimod, the latest immune response modifier (IRM), has shown in vivo evidence of efficacy against herpes simplex virus (HSV) type 2. The first clinical trial involving resiquimod demonstrated that it reduced the recurrence rate of genital herpes, but phase III trials were suspended due to lack of efficacy. Resiquimod shows promise for other viral infections and as a vaccine adjuvant.